Understanding the interplay of membrane trafficking, cell surface mechanics, and stem cell differentiation.

Stem cells can generate a diversity of cell types during development, regeneration and adult tissue homeostasis. Differentiation changes not only the cell fate in terms of gene expression but also the physical properties and functions of cells, e.g. the secretory activity, cell shape, or mechanics. Conversely, these activities and properties can also regulate differentiation itself. Membrane trafficking is known to modulate signal transduction and thus has the potential to control stem cell differentiation. On the other hand, membrane trafficking, particularly from and to the plasma membrane, depends on the mechanical properties of the cell surface such as tension within the plasma membrane or the cortex. Indeed, recent findings demonstrate that cell surface mechanics can also control cell fate. Here, we review the bidirectional relationships between these three fundamental cellular functions, i.e. membrane trafficking, cell surface mechanics, and stem cell differentiation. Furthermore, we discuss commonly used methods in each field and how combining them with new tools will enhance our understanding of their interplay. Understanding how membrane trafficking and cell surface mechanics can guide stem cell fate holds great potential as these concepts could be exploited for directed differentiation of stem cells for the fields of tissue engineering and regenerative medicine.